Affiliation:
1. From the Laboratoire d'Immunologie Cellulaire, Centre de Transfusion Sanguine des Armées Jean Julliard, Clamart Cedex, France; Institut National de la Santé et de la Recherche Médicale, Hôpital Paul Brousse, Villejuif, France; Hôpital d'Instruction des Armées Percy, Clamart Cedex, France.
Abstract
The chemokine stromal cell-derived factor-1 (SDF-1), and its receptor, CXCR-4, have been implicated in the homing and mobilization of human CD34+ cells. We show here that SDF-1 may also be involved in hematopoiesis, promoting the proliferation of human CD34+ cells purified from normal adult peripheral blood (PB). CXCR-4 was expressed on PB CD34+ cells. The amount of CXCR-4 on PB CD34+ cells was 10 times higher when CD34+ cells were purified following overnight incubation. CXCR-4 overexpression was correlated with a primitive PB CD34+ cell subset defined by a CD34high CD38lowCD71lowc-KitlowThy-1+antigenic profile. The functional significance of CXCR-4 expression was ascertained by assessing the promoting effect of SDF-1 on cell cycle, proliferation, and colony formation. SDF-1 alone increased the percentage of CD34+ cells in the S+G2/M phases and sustained their survival. In synergy with cytokines, SDF-1 increased PB CD34+ and CD34highCD38low cell expansion and colony formation. SDF-1 also stimulated the growth of colonies derived from primitive progenitors released from quiescence by anti–TGF-β treatment. Thus, our results shed new light on the potential role of this chemokine in the stem cell engraftment process, which involves migration, adhesion, and proliferation. Furthermore, both adhesion-induced CXCR-4 overexpression and SDF-1 stimulating activity may be of clinical relevance for improving cell therapy settings in stem cell transplantation.
Publisher
American Society of Hematology
Subject
Cell Biology,Hematology,Immunology,Biochemistry
Cited by
304 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献